Breast cancer - pipendoxifene

Genetic factors are believed to play an important role in the development of many breast cancers, and the cancers are hormone-dependent.

Some forms require a low level of oestrogen to survive and grow, so if this oestrogen is removed then the tumour will shrink. Selective oestrogen receptor modulators (SERMs) have proved important in the treatment of breast cancer, and even in its prevention, with tamoxifen therapy being a standard follow-up treatment for women recovering from oestrogen-dependent breast cancer.

However, around 90% of women with metastatic cancer will develop resistance to tamoxifen within a year, and some patients are inherently resistant to it. SERMs have agonist effects in some forms of tissue and antagonist effects in others, and the various SERMs that have been developed over the past decade have different pharmacological profiles.

Wyeth is developing a new SERM, pipendoxifene, formerly referred to as ERA 923, along with Ligand Pharmaceuticals. It has been shown to have a potent, selective oestrogen modulating effect, with few uterine side-effects.¹

Two randomised double blind placebo-controlled trials have been carried out in healthy post-menopausal women to establish its safety and pharmacokinetics. In one, 46 subjects were given a single oral dose of pipendoxifene, in doses ranging between 1mg and 200mg, or a placebo, followed by a 20-day wash out period and then a second, higher dose.² Only minor, short-term side effects were seen, but it appeared that the drug's bioavailability may decrease as the dose rises.

In the second trial, multiple doses were given orally to 50 subjects. They were administered 10, 50, 100, 150 or 200mg once a day for 28 days or placebo, mostly after overnight fasting. The most frequently reported side effects were headache, pain and hot flushes, though with the exception of pain, this was the same for both groups.³